Hepatocytes deficient in CCAAT/enhancer binding protein alpha (C/EBP alpha) exhibit both hepatocyte and biliary epithelial cell character.

To further elucidate the role of CCAAT/Enhancer Binding Protein alpha (C/EBP alpha) in hepatocyte differentiation, we investigated fetal and newborn C/EBP alpha-deficient (C/EBP alpha -/-) mice using confocal microscopy and markers specific for hepatocyte (AFP) and biliary epithelial cell (A6) differentiation. Histologically, in fetal liver of C/EBP alpha -/- mice, pseudoglandular structures appeared starting at 16.5 days of gestation. In newborn livers, the diameters of these structures greatly increased. They were randomly distributed between portal and central veins and interfered with the establishment of normal hepatic plates. However, the portal bile ducts developed normally. The pseudoglandular structures were lined with small hepatocytes with round nuclei and were positive for both AFP and A6 antigens. These data show that C/EBP alpha -/- hepatocytes exhibit biliary epithelial cell characters and suggest an involvement of C/EBP alpha in the control of the switch in the differentiation of bi-potential hepatoblasts along the hepatocyte lineage.